Institute for Endocrinology and Experimental Oncology, National Research Council, Via Pietro Castellino 111, Napoli, Italy.
Expert Rev Mol Med. 2024 Aug 27;26:e17. doi: 10.1017/erm.2024.13.
ADP-ribosyltransferases of the PARP family encompass a group of enzymes with variegated regulatory functions in cells, ranging from DNA damage repair to the control of cell-cycle progression and immune response. Over the years, this knowledge has led to the use of PARP1/2 inhibitors as mainstay pharmaceutical strategies for the treatment of ovarian, pancreatic, prostate and breast cancers, holding mutations in genes encoding for proteins involved in the DNA repair mechanisms (synthetic lethality). Meanwhile, the last decade has witnessed significant progress in comprehending cellular pathways regulated by mono-ADP-ribosylation, with a huge effort in the development of novel selective compounds to inhibit those PARPs endowed with mono-ADP-ribosylation activity. This review focuses on the progress achieved in the cancer field, delving into most recent findings regarding the role of a subset of enzymes - the interferon-stimulated PARPs - in cancer progression.
聚腺苷二磷酸核糖基转移酶家族中的 PARP 酶包含了一组具有多样化调节功能的酶,这些功能从 DNA 损伤修复到细胞周期进程和免疫反应的控制都有涉及。多年来,这些知识已被用于开发 PARP1/2 抑制剂,作为治疗卵巢癌、胰腺癌、前列腺癌和乳腺癌的主要药物策略,这些癌症都存在编码参与 DNA 修复机制的蛋白质的基因突变(合成致死性)。与此同时,在过去十年中,人们对受单聚腺苷二磷酸核糖基化调节的细胞途径有了更深入的理解,并在开发新型选择性化合物以抑制那些具有单聚腺苷二磷酸核糖基化活性的 PARP 方面取得了巨大进展。这篇综述重点介绍了在癌症领域所取得的进展,深入探讨了一组酶(干扰素刺激的 PARP 酶)在癌症进展中的最新作用。